Urinary Concentrations of Organophosphate Flame Retardant Metabolites and Pregnancy Outcomes among Women Undergoing in Vitro Fertilization

Courtney C Carignan, Lidia Mínguez-Alarcón, Craig M Butt, Paige L Williams, John D Meeker, Heather M Stapleton, Thomas L Toth, Jennifer B Ford, Russ Hauser, EARTH Study Team, Courtney C Carignan, Lidia Mínguez-Alarcón, Craig M Butt, Paige L Williams, John D Meeker, Heather M Stapleton, Thomas L Toth, Jennifer B Ford, Russ Hauser, EARTH Study Team

Abstract

Background: Evidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes.

Objectives: We evaluated associations between urinary concentrations of PFR metabolites and outcomes of in vitro fertilization (IVF) treatment among couples recruited from an academic fertility clinic.

Methods: This analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman.

Results: Detection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ΣPFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%).

Conclusions: Using IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP1021.

Figures

Figure 1.
Figure 1.
Organophosphate flame retardant parent compound and primary urinary metabolite.
Figure 2.
Figure 2.
Adjusted mean [95% confidence interval (CI)] proportion of cycles resulting in implantation, live birth, and clinical pregnancy by quartile of urinary organophosphate flame retardant (PFR) metabolite concentrations among 211 women undergoing 297 in vitro fertilization (IVF) cycles. Gray shading indicates change in means from the first and fourth quartile. Adjusted models control for maternal age (continuous), body mass index (BMI) (continuous), race/ethnicity (black/Asian/other, white/Caucasian), year of IVF treatment cycle (continuous), and primary Society for Assisted Reproductive Technology (SART) infertility diagnosis at study entry (female, male, unknown), with continuous variables at their mean level and categorical variables weighted by their frequency in the study population. *Significantly different from the lowest quartile (Q1) at the α=0.05 level.

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Source: PubMed

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